Cardiac pacing devices, such as cardiac pacemakers, implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices are available to provide pacing therapy to a heart. Early cardiac pacemakers were asynchronous, single-chamber devices that stimulated a ventricle of the heart at a fixed rate, independent of the patient's underlying cardiac rhythm or metabolic demand. Although such pacemakers, typified by U.S. Pat. No. 3,057,356 to Greatbatch, provided a ventricular pacing rate sufficient to sustain life, this pacing mode often competed with native ventricular rhythms.
Subsequently, demand pacemakers (VVI) were developed. This type of pacemaker provide pacing pulses only when spontaneous ventricular activity is absent. U.S. Pat. No. 3,478,746 to Greatbatch demonstrates an example of such a pacemaker. This form of pacemaker provides a ventricular sense amplifier for detecting ventricular depolarizations. A ventricular sensed event resets the pacemaker's ventricular escape interval (V-V) timer. The ventricular sensed event also cancels or inhibits the scheduled ventricular stimulus and thus avoids competition with the native ventricular rhythm.
Atrial synchronized pacemakers (VAT) were developed almost simultaneously with VVI demand pacemakers. This type of pacemaker paces the ventricle in response to a detected atrial rate. The VAT pacemaker, as typified by U.S. Pat. No. 3,253,596 to Keller, provides an atrial sense amplifier for detecting atrial depolarizations. An atrial sensed event starts the pacemaker's A-V delay timer. When the A-V delay timer times out, a ventricular stimulus is provided. Conceptually, such a pacemaker can be considered as a prosthetic conduction pathway that simulates the natural A-V conduction pathways of the heart. One drawback to this form of pacing is the possibility of competing with ectopic ventricular activity. An ectopic ventricular beat (PVC) may be detected in the atrium (i.e., by far-field sensing of a PVC, for example) and classified as an atrial sensed event. In such cases, the pacemaker may begin an AV interval, resulting in the generation of a ventricular stimulus a short time after the ventricular depolarization. Although such a result may have little effect when the A-V delay is short, it is possible to deliver the pacing stimulus into the vulnerable period of the ventricular depolarization response, and thereby possibly initiate a ventricular arrhythmia.
Continued development of pacemakers was marked by the invention of the AV sequential pacemaker (DVI), as disclosed in U.S. Pat. No. 3,595,242 issued to Berkovits. This form of pacemaker can provide stimulation pulses in both the atrium and the ventricle, while providing sensing only in the ventricle. In the DVI mode pacemaker, a ventricular sense event starts a V-A escape interval followed by an A-V interval. The pacemaker delivers an atrial stimulus at the end of the V-A interval and, at the end of the A-V interval, the pacemaker delivers a ventricular stimulus. If a ventricular sense event occurs during the V-A or A-V time intervals, the pacemaker will resynchronize to the ventricular sense event and inhibit the delivery of the scheduled ventricular stimulus.
The DDI mode pacemaker described by U.S. Pat. No. 3,747,604 to Berkovits further includes an atrial sense amplifier to inhibit the atrial stimulus when an atrial sense event occurs during the V-A interval.
However, the atrial sense event does not start an A-V interval; such timing may make this device suitable in patients where atrial competition should be avoided.
The atrial-synchronized ventricular-inhibited or VDD mode pacemaker, as disclosed in U.S. Pat. No. 3,648,707 issued to Greatbatch has mechanisms for sensing in the atrium and ventricle while providing stimulating pulses only in the ventricle. In operation, the VDD pacemaker starts an A-V interval on detected atrial activity and provides a ventricular stimulus if one does not occur within the A-V delay. A ventricular sensed event inhibits the scheduled ventricular stimulus and resets the pacemaker's V-V timer.
The dual sense, dual pace DDD mode pacemakers, have been described in U.S. Pat. No. 4,312,355 issued to Funke. The DDD mode pacemaker, as described by Funke, has had broad applications. This type of pacemaker has sense amplifiers for detecting atrial and ventricular events, as well as output pulse circuitry for stimulating both the atrium and the ventricle. Pacemakers operating in the DDD mode provide timing circuitry to initiate an A-V delay upon the occurrence of an atrial event, whether sensed or paced. If, during the A-V delay period, no spontaneous ventricular event is sensed, the pacemaker will produce a ventricular stimulus at the conclusion of the A-V delay. If, during the V-A interval, no spontaneous atrial event is sensed, the pacemaker provides an atrial stimulus at the conclusion of the V-A interval.
In the DDD pacemaker mode, in the absence of spontaneous P-waves and R-waves, the heart will be stimulated at fixed A-A and V-V intervals with a programmable AV delay. However, if the ventricle depolarizes spontaneously, the A-V delay is truncated and the observed A-A and V-V intervals may vary according to whether “atrial-based” or “ventricular-based” timing (or some modification thereof) is employed. For example, ventricular-based timing attempts to maintain a constant V-V interval such that spontaneous depolarization of the ventricle during the A-V delay may cause the A-A time to be truncated. Alternatively, atrial-based timing attempts to maintain constant A-A intervals such that spontaneous depolarization of the ventricle during the A-V delay may result in a longer V-V interval.
The dual chamber pacemaker modalities, DVI, VAT, VDD and DDD, attempt to restore A-V synchrony and thus improve cardiac output by ensuring the hemodynamic contribution of the atrial chambers within the pacing regimen. The latter three modes may also synchronize the pacing rate to the patient's native atrial or sinus rate and thus may provide an increased pacing rate in response to bodily activity, thereby increasing cardiac output.
More recently, other pacemakers, which increase cardiac output in response to exercise, have been proposed. They include pacemakers that rely upon the sensing of physical activity via an activity sensor or accelerometer, changes in blood pH, respiratory rate, or QT interval. These data are used to alter the pacemaker's escape intervals, and hence the pacing rate.
An example of an activity responsive pacemaker is described in U.S. Pat. No. 4,428,378, issued to Anderson et al., and incorporated by reference herein. The pacemaker disclosed in that patent monitors the physical activity of the patient and increases the pacing rate in response to an increase in patient physical activity.
U.S. Pat. No. 4,890,617 issued to Markowitz et al., incorporated herein by reference, describes a dual chamber activity responsive pacemaker that senses and paces in both the atrium and the ventricle. The pacing rate is determined by the sensed activity of the patient, the programmed lower rate, and the patient's atrial or sinus rate.
U.S. Pat. No. 4,932,046, entitled “Dual Chamber Rate Responsive Pacemaker,” assigned to Medtronic, Inc. of Minneapolis, Minn., which is herein incorporated by reference in its entirety, describes a dual chamber rate responsive pacemaker. The pacemaker operates in an atrial-synchronized modality when the sensed atrial rate is present (i.e., above a sensor-determined rate), and paces at the sensor-determined rate when the sensed atrial rate is absent or below the sensor-determined rate.
DDD pacemakers are often implanted in patients with Sick Sinus Syndrome (SSS), a term that covers a large array of sinus node disease states. Such patients often have intact AV conduction and, if the pacemaker's AV interval is not properly programmed, the pacemaker will deliver an unneeded and undesirable ventricular pacing pulse. Many patients who receive DDD pacemakers (or dual-chamber ICDs with DDD pacing capability) are unnecessarily paced in the ventricle. There appears to be reluctance in the medical community against implanting a DDD device and programming it to the AAI/R mode in patients with sick sinus syndrome (SSS) and intact AV conduction; this reluctance may be due to concerns with transient AV block, for example. Moreover, when programmed to the DDD mode, the AV intervals in these pacemakers may be left at their factory-programmed state, that is, with shorter durations more suitable to third degree AV block patients. As a result, ventricular pacing frequently occurs at the termination of these AV intervals, with little or no possibility of spontaneous ventricular activity occurring.
There is growing medical evidence that inappropriate ventricular pacing may impact hemodynamics and may not be beneficial when allowed to continue for an extended period of time. It has been known in the art as early as 1925 that ventricular pacing results in asynchronous delayed activation of the ventricular tissue and, thereby, produces compromised hemodynamics in mammals. More recently, canine studies have shown that right ventricular apical (RVA) pacing causes a negative “inotropic effect” and a >30% reduction in cardiac efficiency. In addition, long term RVA pacing has been shown to lead to permanent changes including myofibrillar cellular disarray, myocardial perfusion defects, and structural abnormalities. Each of these may further contribute to deterioration of ventricular function.
Various cardiac pacing devices have attempted to address this problem by implementing algorithms that automatically adapt the AV interval duration to preferentially allow AV conduction when present.
In U.S. Pat. No. 5,861,007, issued to Hess, et al, a Search AV operation is described in which the pacemaker continuously monitors for the presence or absence of an intrinsic R-wave after both sensed and paced P-waves. The programmed AV interval may be extended by a programmable “hysteresis” interval to promote ventricular conduction. The extension of the AV interval, however, may be limited in duration due to the interaction with the post-ventricular atrial refractory period (PVARP) at higher rates. This is because the AV interval and the immediately following PVARP together form a Total Atrial Refractory Period (TARP) during which no atrial activity can be sensed (or tracked). Thus, the TARP sets a limit on the maximum rate (the “Upper Rate”) at which the DDD mode can track atrial sensed events. To maintain unimpeded upper rate operation, Search AV may work in conjunction with Auto-PVARP (shortening of the PVARP with increasing rates) to maintain atrial sensing and tracking up to the programmed upper rate limit, thereby postponing a 2:1 block operation as long as possible. Since there is a limit to the shortening of the PVARP in this operation, it may become necessary to shorten the AV interval after the PVARP reaches its minimum value. Consequently, many patients (>30%) with intact AV conduction are ventricularly paced to a significant degree (>50%) despite having Search AV programmed on.
Other approaches to the problem are presented in U.S. Pat. No. 5,318,594 issued to Limousin, et al., and in U.S. Pat. No. 6,122,546 issued to Sholder, et al. Limousin describes a DDD Automatic Mode Switch (AMS) pacemaker that operates in a “Special AAI” mode as long as R-wave sensing occurs within a ventricular surveillance window that is calculated based on the history of the measured PR interval. If an R-wave is not sensed within this window, the pacing operation switches to the DDD mode. After 100 consecutive paced ventricular events, the pacemaker attempts to switch back to the Special AAI mode. Sholder implements a form of AV/PV hysteresis. This operation encourages intrinsic conduction by extending the AV interval by a predetermined period beyond the programmed duration. As indicated above, this operation may be restricted to avoid interaction with upper rate tracking.
AV extension algorithms present unique challenges in dual chamber ICDs due to the added requirements of tachyarrhythmia detection. For example, to adequately detect a ventricular tachycardia, the AV delay must be restricted so that the tachycardia detection interval falls within the VA interval at all times. Failure to do so comes at the expense of tachyarrhythmia detection sensitivity. An alternative means to address this issue is by means of a temporary mode change for a programmed period of time following the delivery of a shock. Unfortunately, while this may protect against transient post-shock AV block, it does so at the expense of beat-to-beat monitoring. Consequently, many electrophysiologists do not program the AAI/R mode on a permanent basis to avoid persistent ventricular pacing.
“Ideoventricular kick,” first described by Schlant in 1966, (Circulation, 1966; 23 & 24 (Suppl. III): 209) results from improved coherence of the ventricular contraction during normal activation. This hemodynamic benefit is lost during ventricular pacing. In an earlier study of the atrial contribution to ventricular filling (Kosowski B, et al., Re-evaluation of the atrial contribution to ventricular filling: Study showing his-bundle pacing, Am J Cardiol, 1968; 21 518-24), it was demonstrated that ventricular function was better during normal ventricular activation independent of the PR interval. Similarly, a later study (Rosenqvist M, et al., Relative importance of activation sequence compared to atrioventricular filling synchrony in left ventricular function, Am J Cardiol, 1991; 67(2): 148-56) showed that AAI pacing was superior to either VVI or DDD pacing.
Aside from the hemodynamic benefits mentioned above, it may be that normal ventricular activation has a role in preventing tachyarrhythmias. In a study of 77 ICD patients with a mean follow-up of 18.7 months (Roelke M, et al. Ventricular pacing induced ventricular tachycardia in patients with implantable cardioverter defibrillators. PACE, 1995; 18(3): 486-91), appropriately timed ventricular pacing preceded tachyarrhythmia onset in 8.3% of the episodes in five patients. A further study (Belk P, et al. Does ventricular pacing predispose to ventricular tachycardia? Abstract. PACE, April, 2000) demonstrates that high rate ventricular pacing renders patients more susceptible to the induction of ventricular tachycardia compared to high rate atrial pacing with normal ventricular activation.
More recently, the “Dual Chamber and VVI Implantable Defibrillator” (DAVID) Trial concluded that intrinsic conduction may be more desirable than RV apical pacing, and that patients with indications for implantable defibrillators and no indication for pacing should not be paced in the dual chamber pacing mode. Cardiac Electrophysiology Rev. 2003 December, 7(4):468-72.
These studies, combined with the growing body of evidence showing the detrimental effects of long-term ventricular pacing, has led to more deliberate efforts by clinicians to allow for normal ventricular activation when programming dual chamber bradycardia devices. Still, due to the interactions imposed by PVARP and upper rate timing, mode switching, and tachyarrhythmia detection, their best intentions are often thwarted.
In U.S. Pat. No. 6,772,005 to Casavant, et al., herein incorporated by reference in its entirety, an ADI/R mode is implemented using an intelligent pacing system to continually monitor ventricular response. This pacing mode seeks to ensure AV conduction whenever possible so as to gain all the benefits of cardiac contractile properties resulting from native R-waves. In the event where AV conduction is blocked, the pacing mode is switched to a DDD/R mode to ensure a paced R-wave. Thereafter, subsequent to a completed interval of a p-wave, ADI/R pacing resumes to monitor ventricular response.
Techniques for further enhancing cardiac contractile properties include the use of post-extra systolic potentiation (PESP), described by Burnes, et al., in U.S. Published Pat. App. No. 2004/0220631. Post-extra systolic potentiation (PESP) is a property of cardiac myocytes that results in enhanced mechanical function of the heart on the beats following an extra systolic stimulus delivered early after either an intrinsic or pacing-induced systole. An extra stimulus delivered after an intrinsic systole is referred to as coupled (or triggered) pacing, and an extra stimulus delivered after a pacing-induced systole is referred to as paired pacing. The magnitude of the enhanced mechanical function is strongly dependent on the timing of the extra systole relative to the preceding intrinsic or paced systole. When correctly timed, an extra systolic stimulation pulse causes an electrical depolarization of the heart, but the attendant mechanical contraction is absent or substantially weakened. The contractility of the subsequent cardiac cycles, referred to as the post-extra systolic beats, is increased as described in detail in commonly assigned U.S. Pat. No. 5,213,098 issued to Bennett et al., incorporated herein by reference in its entirety.
As noted, the degree of mechanical augmentation on post-extra systolic beats depends on the time interval between a primary systole and the subsequent extra systole, referred to herein as the “extra stimulus interval” (ESI). If the ESI is too long, the PESP effects are not achieved because a normal mechanical contraction takes place in response to the extra systolic stimulus. As the ESI is shortened, a maximal effect is reached when the ESI is slightly longer than the myocardial refractory period. An electrical depolarization occurs without a mechanical contraction or with a substantially weakened contraction. When the ESI becomes too short, the stimulus falls within the absolute refractory period and no depolarization occurs. The use of an appropriately timed PESP extra stimulus in the atrium may be used to effect a slowing of the rate of intrinsic atrial contractions due to resetting of the sinus node. A PESP extra stimulus in the ventricle may occasionally prevent an atrial depolarization from conducting to the ventricles.
As indicated in the above-referenced '098 patent, one potential risk associated with delivering extra systolic stimulation pulses to achieve PESP is the potential for arrhythmia induction. If the extra systolic pulse is delivered to cardiac cells during the vulnerable period, the risk of inducing tachycardia or fibrillation in arrhythmia-prone patients may be high. The vulnerable period encompasses the repolarization phase of the action potential, also referred to herein as the “recovery phase,” and a period immediately following it.
What is needed, therefore, is a method of providing cardiac pacing therapy at an appropriate rate that includes the mechanical augmentation benefits of PESP, while maximizing the opportunity for intrinsic AV conduction.